one of the key things to do during the transition from preclinical development studies to clinical development studies is to set the target for your drug assay limit of quantification (LOQ). I will outline a few considerations on that topic. Here are my main assumptions:
- You are working with a drug that is intended for systemic delivery (not a local drug like topical dermatological or ophthalmic)
- You have some exposure data from preclinical species
- You have estimated a peak human exposure using some method (e.g. allometry)
To set your target LOQ, you use the expected peak human exposure. Let’s assume the following for our example:
Predicted Cmax = 250 ng/mL
You will need at least 5 half-lives after the peak occurs to accurately calculate the terminal elimination rate constant. You can calculate how much drug remains after 5 half-lives using the following equation:
This gives a reasonable estimate for the LOQ. In this case, I would round down to 1 ng/mL as my initial target LOQ with a stretch goal of trying to achieve 0.1 ng/mL in case my human prediction was high.
That’s all there is to it!